Internal medicine - Clinical genetics Flashcards
INT - 16.1
Among the following monogenic diseases predisposing for tumorigenesis which one is not autosomal dominantly inherited?
A) multiple endocrine neioplasia type 1
B) von Hippel–Lindau disease
C) ataxia teleangiectasia
D) multiple endocrine neioplasia type 2
E) neurofibromatosis type 1
ANSWER
C) ataxia teleangiectasia
EXPLANATION
The majority of monogenic tumor syndromes are autosomal dominantly inherited as multiple endocrine neoplasias type 1 and 2, von Hippel-Lindau disease and the most prevalent monogenic tumor syndrome, neurofibromatosis type 1. Ataxia teleangiectasia predisposes to lymphoma and cerebellar degeneration. The error of DNA repair enzymes leads to the formation of ataxia teleangiectasia, Bloom-syndrome, xeroderma pigmentosum, Fanconi-anaemia ataxia teleangiectasia all of which are autosomal recessively inherited.
INT - 16.2
At which pregnancy age is amniocentesis recommended?
A) 4–6 weeks
B) 10–12 weeks
C) 15–17 weeks
D) 20–22 weeks
E) 24–26 weeks
ANSWER
C) 15–17 weeks
EXPLANATION
Amniocentesis is regularly performed at 15-17 weeks of pregnancy.
INT - 16.3
Among the following chromosome abnormalities which one is the most frequent?
A) Turner-syndrome
B) Edwards-syndrome
C) Down-syndrome
D) Patau-syndrome
E) Williams-syndrome
ANSWER
C) Down-syndrome
EXPLANATION
Among the listed chromosome abnormalities Down syndrome is the most frequent with an incidence in live-borns of approximately 1:800. The other listed chromosome abnormalities are much rarer.
INT - 16.4
What does the term penetrance mean?
A) the frequency of a genetic alteration
B) the frequency of a certain phenotype int he case of a certain genotype
C) a form of genetic regulation
D) the expression of small molecular weight RNAs
E) region of chromosomal regulation
ANSWER
B) the frequency of a certain phenotype int he case of a certain genotype
EXPLANATION
Penetrance means the ”power” of a certain genotype to produce a certain phenotype and show how frequent a certain phenotype is in case of a certain genotype. Some diseases are characterized by high penetrance (e.g. medullary thyroid cancer in the case of multiple endocrine neoplasia type 2 is present in approximately 100%) while other diseases have low penetrance (in the case of haemochromatosis only 1%).
INT - 16.5
What proportion of the human genome is protein-coding?
A) 3%
B) 10%
C) 25%
D) 40%
E) 60%
ANSWER
A) 3%
EXPLANATION
The proportion of protein-coding regions in the human genome is only 3%. Previously, the rest 97% was considered ”junk DNA” not having any relevance in gene expression. However, recent data confirmed important regulatory regions within this 97% and utmost importance of the non-coding genome in species specificity and variability has been shown as well.
INT - 16.6
Which one of the following diseases has the lowest penetrance?
A) multiple endocrine neoplasia type 1
B) multiple endocrine neoplasia type 2
C) neurofibromatosis type 1
D) cystic fibrosis
E) haemochromatosis
ANSWER
E) haemochromatosis
EXPLANATION
The penetrance of haemochromatosis is the lowest (under 1%), all of the others have higher penetrance (some components of multiple endocrine neoplasias, as medullary thyroid cancer in MEN2 or primary hyperparathyroidism in MEN1 are characterized with approximately 100% penetrance). Haemachromatosis may arise due to mutations in multiple genes (HFE, hepcidin, hemojuvelin), however in case of a mutation, only a fraction of patients presents symptoms. Therefore the genetic screening for haemochromatosis is not recommended.
INT - 16.7
Which one of the following diseases does not predispose to pheochromocytoma?
A) von Hippel–Lindau disease
B) Gardner syndrome
C) multiple endocrine neoplasia type 2
D) neurofibromatosis type 1
E) inherited paraganglioma syndromes
ANSWER
B) Gardner syndrome
EXPLANATION
Interestingly, monogenic tumor syndromes are in the background of 25-30% of sporadically observed pheochromocytomas. Multiple endocrine neoplasia type 2, von Hippel-Lindau disease, neurofibromatosis type 1 and inherited paraganglioma syndromes all predispose to pheochromocytoma, with inherited paraganglioma syndromes specifically predispose to extraadrenal pheochromocytoma (paraganglioma). However, Gardner syndrome which predisposes to gastrointestinal polyposis does not predispose to pheochromocytoma.
INT - 16.8
By definition, what is the frequeny of a mutation?
A) < 1%
B) < 5 %
C) < 10%
D) < 20%
E) < 30%
ANSWER
A) < 1%
EXPLANATION
By definition the frequency of a mutation in the population is under 1%
INT - 16.9
What does the term compound heterozygosity mean?
A) More mutations are responsible for a certain disease in autosomal dominantly inherited syndrome.
B) The importance of Y chromosome alterations in sex-linked inheritance.
C) In the case of autosomal recessively inherited disease, different mutations on different allelles of the same gene are jointly responsible for the develeopment of the disease.
D) A rare regulatory mechanism in the case of X-linked dominant inheritance
E) The emergence of different pheotypes due to different mutations int he case of autosomal recessively inherited diseases.
ANSWER
C) In the case of autosomal recessively inherited disease, different mutations on different allelles of the same gene are jointly responsible for the develeopment of the disease.
EXPLANATION
In the case of compound heterozygosity two different mutaions are present on the two different alleles of the same gene. It occurs in cases of autosomal recessively inherited diseases. As with homozygote mutants, both alleles harbor disease-causing mutations, however the mutations differ. In the case of compound heterozygosity blood relations between the parents are not likely.
INT - 16.10
Which pattern of inheritance is characteristic to blood relation between parents?
A) autosomal dominant
B) autosomal recessive
C) X-linked dominant
D) X-linked recessive
E) polygenic
ANSWER
B) autosomal recessive
EXPLANATION
In the case of blood relation between parents the chance of presence of two rare, recessively inherited alleles of the same gene is higher than in the general population. Therefore, blood relation between parents is more common in cases of autosomal recessively inherited diseases.
INT - 16.11
What is the chance of the emergence of an autosomal recessively inherited disease in the offspring of two heterozygote carriers?
A) 10%
B) 25%
C) 40%
D) 50%
E) 60%
ANSWER
B) 25%
EXPLANATION
In the case of autosomal recessive inhertiance, the possibility of the inheritance of the mutant allele from two healthy heterozgote parents is 50-50%. The possibility of the inheritance of two mutant alleles is 0.5×0.5 = 0.25 = 25%. Therefore, statistically in one quarter of the offspring will the disease emerge.
INT - 16.12
What is the chance of emergence of an autosomal dominantly inherited disease in one child of an affected heterozygote individual?
A) 10%
B) 25%
C) 40%
D) 50%
E) 60%
ANSWER
D) 50%
EXPLANATION
A heterozygote individual passes over the mutant allele with 50% chance to the offspring. Since in the case of autosomal dominantly inherited disease the presence of only one damaged allele is enough for the emergence of the disease, the inheritance of the disease is 50% as well.
INT - 16.13
For which mode of inheritance is the following statement true: of the offspring of an affected male and a healthy female, all sons are healthy and all daughters are affected?
A) X-linked recessive
B) X-linked dominant
C) autosomal recessive
D) autosomal dominant
E) polygenic
ANSWER
B) X-linked dominant
EXPLANATION
The affected male passes his Y chromosome only to his sons, while passes his X chromosome only to his daughters. Therefore, in the case of X-linked dominant inheritance, all sons are healthy, while, due to the inheritance of the damaged X chromosome, all daughters are affected.
INT - 16.14
Among the following diseases, in which case does genomic imprinting not constitute to the pathogenesis?
A) Prader–Willi syndrome
B) Angelman syndrome
C) Beckwith–Wiedemann syndrome
D) cystic fibrosis
ANSWER
D) cystic fibrosis
EXPLANATION
In the case of genomic imprinting, paternal and maternal alleles operate differently on certain gene loci. Genomic imprinting possesses role in the pathogenesis of Prader-Willi syndrome, Angelman syndrome and Beckwith-Wiedemann syndrome, however it does not constitute to the pathogenesis of cystic fibrosis.
INT - 16.15
Over what frequency of occurrence in the general population is a genetic variant considered a polymorphism?
A) 1%
B) 7%
C) 10%
D) 15%
E) 20%
ANSWER
A) 1%
EXPLANATION
A genetic variant is considered a genetic polymorphism if its occurrence is over 1% in the general population
INT - 16.16
The trisomy of which chromosome is the most frequent in live-born new-borns?
A) 13
B) 17
C) 19
D) 21
E) 22
ANSWER
D) 21
EXPLANATION
The most frequent trisomy in live-born new-borns is the trisomy of chromosome 21 (Down syndrome).
INT - 16.17
Which chromosomal abnormality affecting the sex chromosomes has the highest incidence?
A) Turner syndrome
B) Klinefelter syndrome
C) Triple X sydrome (superfemale)
D) 46XX male
E) 46XY female
ANSWER
B) Klinefelter syndrome
EXPLANATION
The incidence of Klinefelter syndrome is 1:500 male live-borns. This is the most fequent chromosomal abnormality affecting the sex chromosomes.
INT - 16.18
For which listed chromosome abnormality are the following symptoms characteristic: immunodeficiency, hypoparathyroidism, congenital heart defect?
A) Cri du chat syndrome
B) DiGeorge syndrome
C) Down syndrome
D) Turner syndrome
E) Prader–Willi syndrome
ANSWER
B) DiGeorge syndrome
EXPLANATION
Upon the damage of chromosome 22 (22q11 deletion) do the symptoms representative of DiGeorge syndrome (congenital heart defects e.g. tetralogy of Fallot and pulmonal atresia, hypoparathyroidism, and immunodeficiency due to thymic aplasia) emerge.
INT - 16.19
Which one of the following symptoms is not characteristic to Turner syndrome?
A) short stature
B) streak gonad
C) primary amenorrhea
D) asthma bronchiale
E) coarctation of the aorta
ANSWER
D) asthma bronchiale
EXPLANATION
Short stature, primary amenorrhea due to streak gonad, congenital heart defect are characteristics of Turner syndrome, while asthma bronchiale is not.
INT - 16.21
Amog the following diseases which one is not autosomal dominantly inherited?
A) Marfan syndrome
B) cystic fibrosis
C) Huntington’s disease
D) familial adenomatosus polyposis
E) hereditary retinoblastoma
ANSWER
B) cystic fibrosis
EXPLANATION
Cystic fibrosis is autosomal recessively inherited while Marfan syndrome, Huntington’s disease, familial adenomatosus polyposis and hereditary retinoblastoma are autosomal dominantly inherited.